Page 1112 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

1044 SECTION | XV Mycotoxins

VetBooks.ir H 3 C 9 10 H 11 O H O H 3 R 1 Trichothecenes can be inactivated by strongly acidic and
alkaline conditions. Because of their chemical stability,
trichothecenes are resistant to milling and food processing
H 8 6 13 and readily enter the animal feed and human food chains
7 5 12 4
15 R 2 (JECFA, 2001). Foodborne trichothecene contamination,
R 5 CH 2 in particular DON, has been linked to acute human toxi-
R 4 CH 3 H
R 3 coses in China, India and Japan, however little informa-
tion is available regarding potential health effects from
H H H chronic exposure (Bhat et al., 1989; Kuiper-Goodman,
H C O 1994).
3
R 1
O Key features of mammalian and avian toxicokinetics:
In general, trichothecenes are lipophilic and are readily
O R 2 absorbed across the gastrointestinal tract, and respiratory
mucosae (Wannemacher and Wiener, 1997). Absorption
CH 2
R 4 CH 3 H
R 3 through the skin occurs (particularly with T-2 toxin) but
is slow. Distribution is wide, rapid and usually without
tissue accumulation. The liver is the major site of metabo-
H H
H C O lism. Phase I hydrolysis and oxidation and phase II glucu-
3
ronide conjugation occur in the body tissues; however,
O
reduction of the 12,13-epoxide (deepoxidation) is gener-
O H ally due to gut microfloral metabolism. The exception is
H T-2 toxin where the four basic reactions or pathways
CH 3 OCOCH CHCH 3 occur simultaneously in the same animal (Swanson and
Corley, 1989). Deepoxidation is critical step in detoxifica-
H H H tion of trichothecenes. Acetylation and/or hydrolysis reac-
H C O tions catalyzed by hepatic nonspecific microsomal
3
H
O carboxyl esterase are usually rapid.
Orally administered trichothecenes do not accumulate
to a significant extent in the body. Elimination is rapid
CH 2 H (plasma T 1 /2 2 4 h with elimination mostly completed
CH 3 O
O R within 48 72 h) (Swanson and Corley, 1989). Biliary and
renal excretion are the most important elimination
FIGURE 75.1 Core chemical structure of trichothecenes. pathways.
Poultry have a greater tolerance to trichothecenes than
mycotoxin) production by the same fungi requires high monogastric mammals because of poor absorption follow-
oxygen levels (Miller, 2002). Fusarium occurrence has ing oral exposure, extensive metabolism, and rapid elimi-
increased with the practice of no-till farming and utilizing nation from the body (Prelusky et al., 1986b).
corn in crop rotations. All trichothecenes are cytotoxic and do not require
Trichothecenes also occur in hay, green feed, straw metabolic activation for toxicity to occur.
and silage, particularly when hay is baled wet or stored Excretion into milk and eggs: Lactating cows or laying
under high moisture conditions (.20%; Mostrom et al., hens consuming elevated concentrations of DON transfer
2005). Fungal growth in silage usually takes place on the low to minimal concentrations of DON to the milk or eggs
front edges of silage in bunker silos or where silage is not (Charmley et al., 1993; Co ˆte ´ et al., 1986; El-Banna et al.,
adequately packed allowing aerobic conditions to exist. 1983; Prelusky et al., 1984; Valenta and Da ¨nicke, 2005).
Under these conditions, hay, straw, or silage from Excretion of T-2 toxin into cow’s milk is also usually low
Fusarium-contaminated wheat, barley, oats and corn can (Robison et al., 1979). Gla ´vits and Va ´nyi (1995) described
contain high levels of trichothecenes, particularly DON a “perinatal form of T-2 toxicosis” in swine in Hungary.
and its acetylated metabolites. T-2 toxin excretion in milk was associated with character-
Factors allowing the persistence of trichothecenes in istic T-2 lesions and mortality in the suckling piglets.
the food chain: Trichothecenes are stable when exposed Microbial metabolism: Substantial rumen microflora-
to air, light or both (Wannemacher and Wiener, 1997). mediated rumen metabolism (predominantly detoxifica-
They are not inactivated by normal autoclaving and ther- tion by deepoxidation) occurs (Co ˆte ´ et al., 1986; Da ¨nicke
mal inactivation requires heating at high temperatures for et al., 2005; He et al., 1992; Kiessling et al., 1984; King

relatively long periods of time (e.g., 482 C for 10 min). et al., 1984; Prelusky et al., 1986a; Westlake et al.,